TY - JOUR
T1 - Safety and efficacy of C1-inhibitor in traumatic brain injury (CIAO@TBI)
T2 - study protocol for a randomized, placebo-controlled, multi-center trial
AU - van Erp, Inge A. M.
AU - van Essen, Thomas A.
AU - Fluiter, Kees
AU - van Zwet, Erik
AU - van Vliet, Peter
AU - Baas, Frank
AU - Haitsma, Iain
AU - Verbaan, Dagmar
AU - Coert, Bert
AU - de Ruiter, Godard C. W.
AU - Moojen, Wouter A.
AU - van der Jagt, Mathieu
AU - Peul, Wilco C.
N1 - Funding Information: This project is financially funded by the Hersenstichting Nederland (Dutch Brain Foundation, grant number DR-2019-00292). Takeda Development Center Americas, Inc. funds by providing the trial intervention (Request ID: IIR-NLD-002790). The funding bodies have no role in the design of the study; collection, management, analysis, and interpretation of the data; writing of the report; and the decision to submit the report for publication. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background: Traumatic brain injury (TBI) is a major cause of death and disability across all ages. After the primary impact, the pathophysiologic process of secondary brain injury consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system could therefore be a therapeutic target in TBI. Objective: To study the safety and efficacy of C1-inhibitor (C1-INH) compared to placebo in patients with TBI. By temporarily blocking the complement system, we hypothesize a decrease in the posttraumatic neuroinflammatory response resulting in a less unfavorable clinical outcome for TBI patients. Methods: CIAO@TBI is a multicenter, randomized, blinded, phase II placebo-controlled trial. Adult TBI patients with GCS < 13 requiring intracranial pressure (ICP) monitoring will be randomized, using block randomization, within 12 h after trauma to one dose 6000 IU C1-INH or placebo. A total of 106 patients will be included, and follow-up will occur up to 12 months. The primary endpoints are (1) Therapy Intensity Level (TIL) Scale, (2) Glasgow Outcome Scale-Extended (GOSE) at 6 months, and (3) complication rate during hospitalization. Outcomes will be determined by a trial nurse blinded for the treatment allocation. Analyses will be conducted in an intention-to-treat analysis. Discussion: We expect that C1-INH administration will be safe and potentially effective to improve clinical outcomes by reducing neuroinflammation in TBI patients. Trial registration: ClinicalTrials.gov NCT04489160. Registered on 27 July 2020. EudraCT 2020-000140-58.
AB - Background: Traumatic brain injury (TBI) is a major cause of death and disability across all ages. After the primary impact, the pathophysiologic process of secondary brain injury consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system could therefore be a therapeutic target in TBI. Objective: To study the safety and efficacy of C1-inhibitor (C1-INH) compared to placebo in patients with TBI. By temporarily blocking the complement system, we hypothesize a decrease in the posttraumatic neuroinflammatory response resulting in a less unfavorable clinical outcome for TBI patients. Methods: CIAO@TBI is a multicenter, randomized, blinded, phase II placebo-controlled trial. Adult TBI patients with GCS < 13 requiring intracranial pressure (ICP) monitoring will be randomized, using block randomization, within 12 h after trauma to one dose 6000 IU C1-INH or placebo. A total of 106 patients will be included, and follow-up will occur up to 12 months. The primary endpoints are (1) Therapy Intensity Level (TIL) Scale, (2) Glasgow Outcome Scale-Extended (GOSE) at 6 months, and (3) complication rate during hospitalization. Outcomes will be determined by a trial nurse blinded for the treatment allocation. Analyses will be conducted in an intention-to-treat analysis. Discussion: We expect that C1-INH administration will be safe and potentially effective to improve clinical outcomes by reducing neuroinflammation in TBI patients. Trial registration: ClinicalTrials.gov NCT04489160. Registered on 27 July 2020. EudraCT 2020-000140-58.
KW - C1-inhibitor
KW - Neuroinflammation
KW - Randomized controlled trials
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85120748602&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13063-021-05833-1
DO - https://doi.org/10.1186/s13063-021-05833-1
M3 - Article
C2 - 34863258
SN - 1745-6215
VL - 22
JO - Trials
JF - Trials
IS - 1
M1 - 874
ER -